Montmorillonite clay-catalyzed one-pot synthesis of α-amino phosphonates

Article abstract of DOI:10.1055/s-2001-15162

α-Aminophosphonates are synthesized by three component condensation of aldehydes, amines and diethyl phosphite using montmorillonite KSF under microwave irradiation in solvent-free conditions to afford enhanced yields and reduced reaction times compared t

Full text of DOI:10.1055/s-2001-15162

LETTER
1131
Montmorillonite Clay-Catalyzed One-Pot Synthesis of -Amino
Phosphonates#
Jhillu S. Yadav,* Basi V. Subba Reddy, Ch. Madan
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
Fax +91 40 7170512; E-mail: yadav@iict.ap.nic.in
Received 23 April 2001
cesses convenient, more economic, environmentally
benign and act as both Bronsted and Lewis acids in their
natural and ion-exchanged forms, enabling them to func-
tion as efficient catalysts for various transformations.10
Further, solvent-free microwave assisted reactions11 have
gained more popularity as they provide an opportunity to
work with open vessels. This avoids the risk of develop-
ment of high pressure and provides a possibility of upscal-
ing the reaction on a preparative scale and helps the
induction of the reaction under dry conditions.
Abstract: -Aminophosphonates are synthesized by three compo-
nent condensation of aldehydes, amines and diethyl phosphite using
montmorillonite KSF under microwave irradiation in solvent-free
conditions to afford enhanced yields and reduced reaction times
compared to conventional methods.
Key words: montmorillonite KSF, -aminophosphonates, micro-
wave irradiation
-Amino phosphonates are an important class of biologi-
cally active compounds1 and their synthesis has received
an increasing amount of interest because of their structural
analogy to -amino acids. Also, -aminophosphonates act
as peptide mimics,2 enzyme inhibitors,3 antibiotics and
pharmacologic agents.4 Generally, they are prepared from
the addition of phosphorous nucleophiles to imines in the
presence of either a base or an acid. Lewis acids such as
SnCl4, BF3 OEt2, ZnCl2, and MgBr2 have been used for
this transformation.5,6 However, these reactions cannot be
carried out in a one-pot operation with a carbonyl com-
pound, amine and diethyl phosphite, because the amines
and water that exist during imine formation can decom-
pose or deactivate the Lewis acids.6 In order to circumvent
some of these problems recently one-pot procedures have
also been developed for this conversion using lanthanide
triflates7 and indium trichloride8 as catalysts. Although,
these procedures do not require the isolation of unstable
imines prior to the reactions, longer reaction times (10-20
hours) are required to obtain the desired products in good
yields. In addition, the use of harmful organic solvents is
undesirable from the view of today’s environmental con-
sciousness. Further, metal triflates7 are found to be effec-
tive for the reactions with aldehydes and not with ketones
and also they are highly expensive. In recent years, the use
of solid acidic catalysts such as clays and zeolites has re-
ceived considerable attention in different areas of organic
synthesis9 because of their environmental compatibility,
reusability, greater selectivity, operational simplicity,
non-toxic, non-corrosiveness, low cost and ease of isola-
tion. Particularly, clay catalysts make the reaction pro-
In this communication, we wish to report a novel and
highly efficient procedure for the synthesis of -amino
phosphonates using an inexpensive and reusable catalyst,
montmorillonite KSF under microwave irradiation.
The reaction of benzaldehyde, benzylamine and diethyl
phosphite in the presence of KSF clay resulted in the for-
mation of -amino phosphonate in 90% yield after 3 min-
utes irradiation under microwaves. Similarly various
aldehydes and amines were reacted with diethyl phosphite
to afford the corresponding -amino phosphonates in high
yields. The reactions proceeded smoothly in solvent - free
conditions and completed within 3-5 min of reaction time.
Both aromatic and aliphatic aldehydes provided excellent
yields of products (80-92%) in a short reaction time
whereas ketones gave phosphanates in good yields (65-
80%) after a longer irradiation time (6-8 min). Several ar-
omatic, , -unsaturated, heterocyclic and aliphatic alde-
hydes worked well to give the phosphonates in high
yields. The advantage of the use of clay catalyst for this
transformation is that KSF clay was easily recovered by
filtration, washed with methanol and reused after activa-
tion at 120 C for 3-4 hours. The reactions of several alde-
hydes, amines and diethyl phosphite were examined in the
presence of KSF clay and the results were summarized in
the Table. The reactions were carried out under micro-
wave as well as thermal conditions. When the reactions
were carried out conventionally in refluxing toluene they
took longer reaction times to achieve good yields of prod-
ucts. Whereas under microwave irradiation the reactions
Scheme 1
Synlett 2001, No. 7, 1131–1133 ISSN 0936-5214 © Thieme Stuttgart · New York

1132
J. S. Yadav et al.
LETTER
were completed in a short reaction time with excellent In conclusion the paper describes a facile synthesis of
yields. The reaction temperature was controlled in a mi- -amino phosphonates using montmorillonite KSF under
crowave oven by pulsed irradiation (1 min with 20 s inter- microwave as well as thermal conditions. The method of-
vals). The temperature was measured at the end of each fers several advantages including high yields of products,
pulsed irradiation. The lowest observed temperature was very short reaction times, cleaner reactions, greater selec-
75 C after one minute irradiation at 450 W and the high- tivity, inexpensive catalyst, ease of isolation of the prod-
est temperature was 105 C after 3 min irradiation at the ucts, regeneration of the catalyst and solvent-free
same power. The reaction rates and yields were dramati- conditions which makes the reaction process convenient,
cally enhanced by microwave irradiation. Further, the re- more economic and environmentally benign.
actions proceeded only to a minor extent (10-15%) when
the reactants were subjected to microwaves in the absence
of KSF clay. Thus, we have compared the reaction rates
Experimental
a) Microwave irradiation: Aldehyde (5 mmol), amine (5 mmol), di-
ethyl phosphite (5 mmol) and montmorillonite (1.5 g, Aldrich,
montmorillonite, KSF) were admixed in a pyrex test tube and ex-
posed to microwave irradiation at 450 W using (BPL, BMO, 700T,
indicates the commertial name of microwave oven) focused micro-
wave oven for an appropriate time (pulsed irradiation 1 min with 20
s interval). After complete conversion of the reaction, as indicated
by TLC, the reaction mixture was directly charged on a small silica
gel column and eluted with a mixture of ethyl acetate-hexane (3:7)
to afford corresponding pure -amino phosphonate.
and yields under microwave as well as thermal conditions.
All the products were characterized by 1H NMR, IR, and
mass spectral analysis and also by comparison with au-
thentic samples.
Table Clay-catalyzed one-pot synthesis of -amino phosphonates
b) Conventional method: A mixture of aldehyde (5 mmol), amine
(5 mmol), diethyl phosphite (5 mmol) and montmorillonite clay (1.5
g) was refluxed in toluene (20 ml) for an appropriate time (Table).
On completion, the reaction mixture was filtered and purified by
column chromatography on silica gel (Merck, 100-200 mesh, ethyl
acetate-hexane, 3:7) to afford pure -amino phospohonate. Repre-
1
sentative spectroscopic data for compound. 4g: liquid, H NMR
(CDCl3) : 1.15 (t, J = 7.0Hz, 3H), 1.25 (t, J = 7.0Hz, 3H), 2.20
(brs, NH), 3.55 (d, J = 14.8 Hz, 1H), 3.70-4.18 (m, 6H), 7.20-7.45
(m, 10H). 13C NMR (Proton decoupled, CDCl3) : 16.09, 16.2,
16.28, 16.40, 51.04, 51.38, 58.12, 61.17, 62.64, 62.79, 62.94,
127.05, 127.83, 128.26, 128.56, 128.68, 129.3, 130.05, 136.0,
146.7. 31P NMR (CDCl3) : 24.007. FAB Mass: m/z: 333 M+, 281,
196, 147, 123, 109, 91, 69, 55.
References and Notes
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a Microwave irradiation was carriedout at 450 W using BPL, BMO,
700T microwave oven by pulsed irradiation technique (20 s interval
for each min.) b Conventional heating in refluxing toluene
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LETTER
Montmorillonite Clay-Catalyzed One-Pot Synthesis of -Amino Phosphonates
1133
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